The subject matter of the invention described herein is an improved process for the preparation of compounds with general formula (I) and in particular of compound (E,Z) 3-(2-aminoethoxyimino)-androstane-6,17-dione (hereinafter referred to as PST 2744) and their pharmaceutically acceptable salts, 
in which:
n=1-3; R1 and R2, which may be the same or different, are hydrogen or alkyl C1-C3 or together form a 5 or 6 term saturated heterocycle, optionally containing a second heteroatom selected from the group consisting of oxygen, sulphur or nitrogen.
The formula (I) compound in which n=1 and R1=R2=H is PST 2744; it is a known compound, endowed with positive inotropic activity at the cardiovascular system level, and is therefore a useful agent in the treatment of heart failure.
European Patent Application EP 0825197 (Sigma-Tau Industrie Farmaceutiche Riunite) discloses PST 2744 and its analogues included in formula (I) above and in addition describes a process for their preparation; PST 2744 is described in the example of preparation no. 7.
The process for the preparation of PST 2744 according to the method described in EP 0825197 is indicated in the following reaction diagram, 
where: TBS=t-butyldimethylsilane; Ac=acetyl
Diagram 1 shows that the process for the preparation of PST 2744, which is done using dehydroepiandrosterone as the starting product, involves as many as 9 steps with the formation of 8 intermediate compounds. This process involves such a large number of steps because protection/deprotection reactions are used for the potentially reactive functional groups present in the molecule.
Such protection is a well-known practice (see, for example: Greene, T. W. and Wuts P. G. M., Protective Group in Organic Synthesis, 3rd ed., Wiley, New York, US, 1999) and is often unavoidable in the field of organic chemistry, but with the drawback that the introduction and subsequent removal of each protective group means lengthening the synthesis process by two steps, with obvious increases in terms both of execution times and costs.
The PST 2744 preparation process described in EP 0825197 is carried out by performig chromatographic purifications of the intermediate products.
An improved process has now been found, and this is the subject matter of the invention described herein, for the preparation of compounds with general formula (I), particularly PST 2744, which avoids the use of protective groups in the various synthesis steps, with a substantial reduction of the number of steps and purifications, and with a substantial reduction of production costs.
The process according to the invention described herein is indicated in the following reaction diagram by way of an example as far as PST 2744 is concerned. 
This process comprises the steps of:
(a) introducing a hydroxyl group in position 6xcex1 of the steroid skeleton and at the same time reducing the ketone function in position 17, obtaining derivative 9 from dehydroepiandrosterone;
(b) oxidating simultaneously the three hydroxyl groups present in derivative 9, obtaining derivative 10;
(c) selectively oximating the ketone group in position 3 of derivative 10 obtaining PST 2744, preferably in a salified form.
It is perfectly clear that the process according to the invention described herein applies to all formula (I) compounds, which differ from one another in the aminoalkyl chain bound to the oxime group in position 3. Given that the addition of the amine aminoalkoxy chain to ketone group 3, to yield the corresponding oximic derivative is analogous to the reaction described in EP 0825197, the process according to the invention, as exemplified for PST 2744 and regarding the transformations on the steroid nucleus, is applicable by analogy to all formula (I) compounds, as described above. Any minor changes made to the reactions exemplified (solvents, molar ratios, reaction controls) are thoroughly obvious and immediate to the technician with average experience in the sector, on the basis of his or her own general knowledge alone.
The advantage of the process according to the invention indicated in Diagram 2 can be immediately perceived on comparing it with the process described in EP 0825197 and indicated in Diagram 1.
Moreover, the process according to the invention described herein takes place with optimum selectivity of oximation of the ketone group in position 3, to yield the compound desired, despite the presence of two other ketone groups in positions 6 and 17.
As has been said, the process according to the invention described herein is characterised by the lack of the use of protective groups. In fact, Diagram 2 shows that from the starting compound, dehydroepiandrosterone, intermediate 10 is obtained in two steps, completely skipping intermediates 1-7 indicated in Diagram 1, in which the protective groups are introduced in steps A and D to yield intermediates 1 and 4, and are then removed in steps E and G to give intermediates 5 and 7.
The reaction conditions used in the process which is the subject matter of the invention described herein, with reference to Diagram 2, are:
Step A: ation of the double bond present in position 5 and reduction of the ketone in position 17 of the dehydroepiandrosterone. For this reaction we use borane (both as a monomer and as the diborane dimer), 9-BBN, disiamylborane or texylborane, both in the free form and as complexes with other substances such as, for example, tetrahydrofuran, dimethylsulphur or bases such as, for example, ammonia, dimethylamine, triethylamine, and pyridine. In particular, the borane can be added to the reaction mixture in the form of a complex with tetrahydrofuran or dimethylsulphur, or can be generated in situ by reaction between sodium borohydride and acetic acid or between sodium borohydride and a Lewis acid, such as, for example, borotrifluoride etherate; or, lastly, it may be generated, in the way previously described, in an environment external to the reaction mixture and can be introduced into said mixture. The reaction is done at a temperature ranging from xe2x88x9210xc2x0 C. to the boiling temperature of the reaction mixture, for a period of time ranging from one to five hours.
The subsequent oxidation of the alkylboranes obtained can be accomplished, for example, with H2O2/NaOH, with sodium perborate or other alkaline perborates added in aqueous solution to the reaction mixture. The reaction is done at a temperature ranging from xe2x88x9210xc2x0 C. to the boiling temperature of the reaction mixture, for a time period ranging from 10 to 24 hours. The final product is purified by crystallisation by solvents such as ethyl acetate, methanol, ethanol, isopropanol, acetone, water or mixtures of the same.
Step B: oxidation of the three hydroxyl functions present in compound 9. This oxidation is carried out with oxidants such as chromium oxide in the presence of sulphuric acid and water (Jones reagent) in acetone, at a temperature ranging from xe2x88x9210xc2x0 C. to the boiling temperature of the reaction mixture; with tetrapropyl-ammonium perruthenate as the oxidant in catalytic amounts and N-methylmorpholine N-oxide as the stoichiometric oxidant, in ethylene chloride or acetonitrile or mixtures of these solvents, optionally in the presence of molecular sieves, at a temperature ranging from xe2x88x9210xc2x0 C. to the boiling temperature of the reaction mixture; ruthenium tetroxide as the oxidant in catalytic amounts, generated in situ from a stoichiometric oxidant, which can be sodium bromate, sodium hypochlorite or an alkaline periodate, such as sodium periodate, starting from ruthenium hydrate dioxide or ruthenium chloride, in solvents such as acetone, acetonitrile/carbon tetrachloride/water, acetonitrile/chloroform/water, acetonitrile/methylene chloride/water, ethyl acetate/acetonitrile/water in variable proportions, at a temperature ranging from xe2x88x9210xc2x0 C. to the boiling temperature of the reaction mixture.
This oxidation reaction described in step B is carried out for a period of time ranging from 0.5 to 24 hours, also depending on the type of oxidant used.
Step C: reaction between triketone 10 and 2-aminoethoxyamine. The reaction is carried out adding the base in salified form or as a free base dissolved in a mixture of solvents such as dioxane, tetrahydrofuran, water or homogeneous mixtures of the same to the reaction mixture containing the triketone in the same solvents as for the base, optionally in the presence of buffer solutions; the pH of the solution may range from approximately 2 to approximately 10 depending on whether or not buffer solutions are used; the reaction temperature ranges from xe2x88x9210xc2x0 C. to the boiling temperature of the reaction mixture and the time period ranges from 0.5 to 12 hours.
The reaction product is isolated for treatment with solvents such as tetrahydrofuran, ethyl alcohol, isopropyl alcohol, ethyl acetate or mixtures of the same. The reaction product can be isolated as a free base or, preferably, as a salt with inorganic acids such as hydrochloric or sulphuric acid or with organic acids such as oxalic acid, fumaric acid or other pharmaceutically acceptable acids. 2-aminoethoxyammine is a known product (Bruno, I. et al. Helv. Chim. Acta, 1962, 45, 358).
On varying the hydroxylamine used, in the last step, compounds of general formula (I) described in the previously cited patent application are obtained.
In this case, the hydroxylamine used has general formula (II): 
in which: n=1-3; R1 and R2 have the meanings described previously.
The hydroxylamines with general formula (II) can be used as free bases or in forms salified with inorganic acids such as hydrochloric acid or sulphuric acid.
The hydroxylamines with general formula (II) are known products, which are often available commercially or can be prepared from commercially available products using standard methods.
The advantages in terms of costs and time which can be achieved with the process that is the subject matter of the invention are therefore obvious.
The process which is the subject matter of the invention described herein is further illustrated by the following examples.